The ultimate goals of this research are to understand the mechanism by which insulin acts to regulate the growth of cells in culture as well as to maintain glucose homeostasis in vivo. Using a cell line which arrests in early GI and can be stimulated to traverse the cell cycle with serum or with physiological concentrations of insulin variations in receptor number per cell will be examined as a function of period of exposure and phase of the cell cycle. The pleiotypic growth responses will be examined with respect to concentration - dependence on insulin, the relationship between concentration-dependency and receptor-occupancy, and the temporal order of appearance of changes in these functions following insulin stimulation. These will be compared with non-growth associated responses to insulin questioning whether these are actually separate functions or are manifestations of insulin function dependent upon the ability of the cell to respond. Other growth factors, particularly FGF,EGF, and IGF (NSILA), will be employed to determine whether there are separate specific growth factor receptors with which may be interacting to elicit the growth response. Finally, because of the unique nature of the response to insulin, it should be possible to select insulin resistant variants which will not release from G1 arrest in response to insulin. With these it should be possible to begin to dissect the insulin response and to determine the elements required for insulin actions on growth and intermediary metabolism.